The overall objective of the project is to develop sustained action injectable biodegradable L-methadone microcapsules which will maintain plasma levels of 200 ng/ml at least one week. Phase I SBIR support is sought for a six month period to conduct preliminary feasibility studies. During Phase I methadone microcapsules will be prepared from several polymers using BIOTEK's air suspension process. Initial emphasis will be placed on formulating a blend of microcapsules prepared from three different polymer compositions. The initial composition of the microcapsule blend formulation will be similar to a microsphere blend formulation which gave a one week zero- order sustained release of l-methadone. This microsphere blend formulation was previously developed by our collaborator Dr. Colin G. Pitt of RTI under a grant from NIDA. Polymers will be characterized by determination of chemical composition, molecular weight and crystallinity. Microcapsules will be evaluated for in vitro L-methadone release kinetics, surface morphology, size distribution, and drug content. The duration of L-methadone release will be determined for selected formulations in rabbits by measuring the plasma level of the drug. These Phase I studies will provide the basis for further development of the formulation in Phase II. The final prototype formulation will be tested in a variety of animals models, and pharmacokinetic studies will be conducted. Documentation will be prepared for an IND application.